Our objective is to determine if systemic and pulmonary vascular reactivity are altered during early experimental diabetes mellitus. We will induce severe diabetes in rats by treating them with streptozotocin. After 1 to 2 months of diabetes, samples of thoracic aorta and of femoral artery will be studied in vitro to determine their contractile reactivity to vasoactive agents such as KC1, angiotensin II, norepinephrine, and prostaglandin F2. If contractile abnormalities are found, various pharmacologic agents will be used to explain the adverse effects of diabetes. Similar in vitro studies will be performed with isolated lungs and pulmonary arteries to allow comparisons between the systemic and pulmonary vasculatures. These studies will provide basic knowledge about the pathogenesis of the vascular diseases that contribute to the morbidity and mortality of patients with diabetes mellitus.